Epigenetic mechanisms such as DNA hypermethylation lead to silencing of tumor suppressor genes and cell cycle regulator genes that influences the efficacy of many anticancer drugs. In addition, cancer cells develop drug resistance. Aberrant DNA methylation is an epigenetic mechanism that leads to silencing of many tumor suppressor genes involved in key DNA damage-response pathways, such as cell cycle control, apoptosis signaling, and DNA repair. This epigenetic silencing influences tumorigenesis, tumor response to drug therapy, and is also the main cause of acquired drug resistance. Drug resistance constitutes lack of response to many chemically and mechanistically unrelated anticancer agents by cancer cells. It is one of the main causes for failure of chemotherapy and can lead to recurrence of the disease or even death. Clinical administration of anticancer drugs can also lead to epigenetic changes in cancer cells such as DNA hypermethylation making them resistant to drug treatment (Nyce, J W, Mutat Res (1997) 386:153-161). Such drug—induced DNA hypermethylation can further create resistance by silencing genes whose products are required by anticancer drugs to execute cytotoxicity.
A need exists to overcome such mechanisms in order to improve cancer treatments.